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1.
Biomater Sci ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38959069

RESUMEN

Hydrogels, as an emerging biomaterial, have found extensive use in the healing of wounds due to their distinctive physicochemical structure and functional properties. Moreover, hydrogels can be made to match a range of therapeutic requirements for materials used in wound healing through specific functional modifications. This review provides a step-by-step explanation of the processes involved in cutaneous wound healing, including hemostasis, inflammation, proliferation, and reconstitution, along with an investigation of the factors that impact these processes. Furthermore, a thorough analysis is conducted on the various stages of the wound healing process at which functional hydrogels are implemented, including hemostasis, anti-infection measures, encouraging regeneration, scar reduction, and wound monitoring. Next, the latest progress of multifunctional hydrogels for wound healing and the methods to achieve these functions are discussed in depth and categorized for elucidation. Finally, perspectives and challenges associated with the clinical applications of multifunctional hydrogels are discussed.

2.
Anal Chem ; 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38975729

RESUMEN

Plant samples with irregular morphology are challenging for longitudinal tissue sectioning. This has restricted the ability to gain insight into some plants using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Herein, we develop a novel technique termed electromagnetic field-assisted frozen tissue planarization (EMFAFTP). This technique involves using a pair of adjustable electromagnets on both sides of a plant tissue. Under an optimized electromagnetic field strength, nondestructive planarization and regularization of the frozen tissue is induced, allowing the longitudinal tissue sectioning that favors subsequent molecular profiling by MALDI-MSI. As a proof of concept, flowers, leaves and roots with irregular morphology from six plant species are chosen to evaluate the performance of EMFAFTP for MALDI-MSI of secondary metabolites, amino acids, lipids, and proteins among others in the plant samples. The significantly enhanced MALDI-MSI capabilities of these endogenous molecules demonstrate the robustness of EMFAFTP and suggest it has the potential to become a standard technique for advancing MALDI-MSI into a new era of plant spatial omics.

3.
Toxics ; 12(6)2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38922091

RESUMEN

The occurrence, distribution, and ecological risk assessment of 36 antibiotics from five groups, including macrolides (MLs), fluoroquinolones (FQs), tetracyclines (TCs), amphenicols (APs), and sulfonamides (SAs), were investigated for the first time in the Anning River, Sichuan Province, China. The results show that antibiotics were widely present in the sediments of the Anning River, with a total of 22 antibiotics detected. FQs were among the most abundant antibiotics, followed by TCs, MLs, APs, and SAs. The total concentrations of antibiotics in surface sediments varied from 0.05 to 53.35 ng/g, with an average of 8.09 ng/g. Among these groups, MLs, FQs, and TCs emerged as the predominant classes of antibiotics. The midstream sediments showed the highest residual levels of antibiotics, with lower levels observed in the downstream and upstream sediments. Anthropogenic activities, such as human clinical practices and animal breeding, might be sources of antibiotics released into the river. An ecological risk assessment revealed that trimethoprim from the SA group exhibited high risks, and MLs showed medium risks in the Anning River, whereas most antibiotics presented minimal to low risks. This study provides valuable information on antibiotic pollution in the upstream region of the Yangtze River, and future management measures are needed for the Anning River.

4.
Heliyon ; 10(11): e31876, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38841472

RESUMEN

Background: Thyroid cancer (TC) is the most common malignant tumor in the endocrine system, is also one of the head and neck tumor. Follicular Thyroid Carcinoma (FTC) plays an important role in the pathological classification of thyroid cancer. This study aimed to develop an innovative predictive tool, a nomogram, for predicting cancer specific survival (CSS) in middle-aged FTC patients. Methods: We collected patient data from the Surveillance, Epidemiology, and End Results (SEER) database. The data from patients between 2004 and 2015 were used as the training set, and the data from patients between 2016 and 2018 were used as the validation set. To identify independent risk factors affecting patient survival, univariate and multivariate Cox regression analyses were performed. Based on this, we developed a nomogram model aimed at predicting CSS in middle-aged patients with FTC. The consistency index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), and the calibration curve were used to evaluate the accuracy and confidence of the model. Results: A total of 2470 patients were enrolled in this study, in which patients from 2004 to 2015 were randomly assigned to the training cohort (N = 1437) and validation cohort (N = 598), and patients from 2016 to 2018 were assigned to the external validation cohort (N = 435) in terms of time. Univariate and multivariate Cox regression analysis showed that marriage, histological grade and TNM stage were independent risk factors for survival. The C-index for the training cohort was 0.866 (95 % CI: 0.805-0.927), for the validation cohort it was 0.944 (95 % CI: 0.903-0.985), and for the external validation cohort, it reached 0.999 (95 % CI: 0.997-1.001). Calibration curves and AUC suggest that the model has good accuracy. Conclusions: We developed an innovative nomogram to predict CSS in middle-aged patients with FTC. Our model after a rigorous internal validation and external validation process, based on the time proved that the high level of accuracy and reliability. This tool helps healthcare professionals and patients make informed clinical decisions.

5.
Hortic Res ; 11(6): uhae100, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38863996

RESUMEN

Horticultural crops comprising fruit, vegetable, ornamental, beverage, medicinal and aromatic plants play essential roles in food security and human health, as well as landscaping. With the advances of sequencing technologies, genomes for hundreds of horticultural crops have been deciphered in recent years, providing a basis for understanding gene functions and regulatory networks and for the improvement of horticultural crops. However, these valuable genomic data are scattered in warehouses with various complex searching and displaying strategies, which increases learning and usage costs and makes comparative and functional genomic analyses across different horticultural crops very challenging. To this end, we have developed a lightweight universal search engine, HortGenome Search Engine (HSE; http://hort.moilab.net), which allows for the querying of genes, functional annotations, protein domains, homologs, and other gene-related functional information of more than 500 horticultural crops. In addition, four commonly used tools, including 'BLAST', 'Batch Query', 'Enrichment analysis', and 'Synteny Viewer' have been developed for efficient mining and analysis of these genomic data.

6.
Ophthalmol Ther ; 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38834934

RESUMEN

INTRODUCTION: Dichoptic training has emerged as a promising rehabilitation approach for improving binocular visual function in patients with strabismus. A prospective observational study design was employed to assess the effectiveness of online video game-based dichoptic training in rehabilitating binocular visual function in patients who had undergone an operation for intermittent exotropia. METHODS: A total of 64 patients who had undergone an operation for intermittent exotropia were recruited and divided into the training group and the control group based on whether they would receive the dichoptic training. The dichoptic training was conducted for 3 months in the training group and the control group would not accept any form of orthoptic therapy. Assessments of binocular visual functions and deviation were conducted at baseline, 3-month and 6-month follow-up. RESULTS: Twenty-nine participants in the training group (mean 9.69 ± 2.66 years old) and 26 participants in the control group (mean 8.41 ± 2.64 years old) completed follow-up. At both 3- and 6-month follow-ups, the training group showed superior distance stereopsis compared to the control group, with near stereopsis only showing significant difference at the 6-month follow-up. Additionally, the training group exhibited significantly less distance exo-deviation drift than the control group at these times, and no significant difference was observed in near exo-deviation drift between the groups. The control group had a significantly higher rate of suboptimal surgical outcomes at both the 3- and 6-month follow-up. However, no significant differences were observed in simultaneous perception and fusion functions between the two groups. CONCLUSIONS: Online video game-based dichoptic training has the potential to become a novel postoperative rehabilitation strategy for patients with intermittent exotropia.

7.
Sci Data ; 11(1): 592, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38844753

RESUMEN

The 'Red Fuji' apple (Malus domestica), is one of the most important and popular economic crops worldwide in the fruit industry. Using PacBio HiFi long reads and Hi-C reads, we assembled a high-quality haplotype-resolved genome of 'Red Fuji', with sizes of 668.7 and 668.8 Mb, and N50 sizes of 34.1 and 31.4 Mb. About 97.2% of sequences were anchored in 34 chromosomes. We annotated both haploid genomes, identifying a total of 95,439 protein-coding genes in the two haplotype genomes, with 98% functional annotation. The haplotype-resolved genome of 'Red Fuji' apple stands as a precise benchmark for an array of analyses, such as comparative genomics, transcriptomics, and allelic expression studies. This comprehensive resource is paramount in unraveling variations in allelic expression, advancing quality improvements, and refining breeding efforts.


Asunto(s)
Genoma de Planta , Haplotipos , Malus , Malus/genética
8.
Mol Biol Rep ; 51(1): 650, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38734811

RESUMEN

BACKGROUND: Vitiligo is a common autoimmune skin disease. Capsaicin has been found to exert a positive effect on vitiligo treatment, and mesenchymal stem cells (MSCs) are also confirmed to be an ideal cell type. This study aimed to explore the influence of capsaicin combined with stem cells on the treatment of vitiligo and to confirm the molecular mechanism of capsaicin combined with stem cells in treating vitiligo. METHODS AND RESULTS: PIG3V cell proliferation and apoptosis were detected using CCK-8 and TUNEL assays, MitoSOX Red fluorescence staining was used to measure the mitochondrial ROS level, and JC-1 staining was used to detect the mitochondrial membrane potential. The expression of related genes and proteins was detected using RT‒qPCR and Western blotting. Coimmunoprecipitation was used to analyze the protein interactions between HSP70 and TLR4 or between TLR4 and mTOR. The results showed higher expression of HSP70 in PIG3V cells than in PIG1 cells. The overexpression of HSP70 reduced the proliferation of PIG3V cells, promoted apoptosis, and aggravated mitochondrial dysfunction and autophagy abnormalities. The expression of HSP70 could be inhibited by capsaicin combined with MSCs, which increased the levels of Tyr, Tyrp1 and DCT, promoted the proliferation of PIG3V cells, inhibited apoptosis, activated autophagy, and improved mitochondrial dysfunction. In addition, capsaicin combined with MSCs regulated the expression of TLR4 through HSP70 and subsequently affected the mTOR/FAK signaling pathway CONCLUSIONS: Capsaicin combined with MSCs inhibits TLR4 through HSP70, and the mTOR/FAK signaling pathway is inhibited to alleviate mitochondrial dysfunction and autophagy abnormalities in PIG3V cells.


Asunto(s)
Apoptosis , Capsaicina , Proliferación Celular , Proteínas HSP70 de Choque Térmico , Melanocitos , Mitocondrias , Transducción de Señal , Serina-Treonina Quinasas TOR , Receptor Toll-Like 4 , Vitíligo , Humanos , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Capsaicina/farmacología , Línea Celular , Proliferación Celular/efectos de los fármacos , Proteínas HSP70 de Choque Térmico/efectos de los fármacos , Proteínas HSP70 de Choque Térmico/metabolismo , Melanocitos/metabolismo , Melanocitos/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Serina-Treonina Quinasas TOR/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Vitíligo/metabolismo , Vitíligo/tratamiento farmacológico , Quinasa 1 de Adhesión Focal/efectos de los fármacos , Quinasa 1 de Adhesión Focal/metabolismo
9.
Invest Ophthalmol Vis Sci ; 65(5): 31, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38771572

RESUMEN

Purpose: Although effective amblyopia treatments are available, treatment outcome is unpredictable, and the condition recurs in up to 25% of the patients. We aimed to evaluate whether a large-scale quantitative contrast sensitivity function (CSF) data source, coupled with machine learning (ML) algorithms, can predict amblyopia treatment response and recurrence in individuals. Methods: Visual function measures from traditional chart vision acuity (VA) and novel CSF assessments were used as the main predictive variables in the models. Information from 58 potential predictors was extracted to predict treatment response and recurrence. Six ML methods were applied to construct models. The SHapley Additive exPlanations was used to explain the predictions. Results: A total of 2559 consecutive records of 643 patients with amblyopia were eligible for modeling. Combining variables from VA and CSF assessments gave the highest accuracy for treatment response prediction, with the area under the receiver operating characteristic curve (AUC) of 0.863 and 0.815 for outcome predictions after 3 and 6 months, respectively. Variables from the VA assessment alone predicted the treatment response, with AUC values of 0.723 and 0.675 after 3 and 6 months, respectively. Variables from the CSF assessment gave rise to an AUC of 0.909 for recurrence prediction compared to 0.539 for VA assessment alone, and adding VA variables did not improve predictive performance. The interocular differences in CSF features are significant contributors to recurrence risk. Conclusions: Our models showed CSF data could enhance treatment response prediction and accurately predict amblyopia recurrence, which has the potential to guide amblyopia management by enabling patient-tailored decision making.


Asunto(s)
Ambliopía , Sensibilidad de Contraste , Recurrencia , Agudeza Visual , Humanos , Ambliopía/terapia , Ambliopía/fisiopatología , Ambliopía/diagnóstico , Agudeza Visual/fisiología , Masculino , Femenino , Sensibilidad de Contraste/fisiología , Niño , Resultado del Tratamiento , Preescolar , Curva ROC , Aprendizaje Automático , Estudios Retrospectivos , Adolescente , Privación Sensorial , Algoritmos
10.
Sci Data ; 11(1): 552, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38811578

RESUMEN

Malus hybrid 'SH6' (M. honanensis × M. domestica)is a commonly used apple interstock in China, known for its excellent dwarfing characteristics and cold tolerance. In this study, a combined strategy utilizing PacBio HiFi, Hi-C and parental resequencing data were employed to assemble two haploid genomes for 'SH6'. After chromosome anchoring, the final hapH genome size was 596.63 Mb, with a contig N50 of 34.38 Mb. The hapR genome was 649.37 Mb, with a contig N50 of 36.84 Mb. Further analysis predicted that repeated sequences made up 59.69% and 62.52% of the entire genome, respectively. Gene annotations revealed 45,435 genes for hapH and 48,261 genes for hapR. Combined with genomic synteny we suggest that the hapR genome originates from its maternal parent M. domestica cv. Ralls Janet, while the hapH genome comes from its paternal parent, M. honanensis. The assembled genome significantly contributes to the discovery of genes associated with apple dwarfing and the molecular mechanisms governing them.


Asunto(s)
Genoma de Planta , Malus , Malus/genética , Cromosomas de las Plantas/genética
11.
Heliyon ; 10(7): e28857, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38596124

RESUMEN

Purpose: To explore the association between the cause of amblyopia and pre-treatment contrast sensitivity, stereoacuity, fixation and nystagmus. Design: Retrospective cohort study. Methods: A retrospective review was conducted for 3408 patients with amblyopia who had not yet started amblyopia treatment utilizing a large amblyopia patient database maintained at Zhongshan Ophthalmic Centre. Six amblyogenic factor subtypes were identified: anisometropia, isoametropia, strabismus, anisometropia and strabismus, monocular visual deprivation, and binocular visual deprivation amblyopia. Monocular best corrected visual acuity (BCVA), the contrast sensitivity function (CSF), fixation, and stereopsis were compared between the subtypes before and after propensity score matching (PSM) for age and sex. Results: The two deprivation groups had poorer BCVA and CSF than the other groups. There were no systematic differences in CSF between the non-deprivation groups. Nystagmus was more common in the bilateral amblyopia groups compared to the monocular amblyopia groups. Eccentric fixation was uncommon with the exception of the anisometropia and strabismus group which had an eccentric fixation rate of 20%. Distance stereoacuity measured without monocular cues was absent for almost all patients. The results were consistent when analyzed using PSM. Conclusion: Visual deprivation causes more severe amblyopia than other amblyogenic factors. For non-deprivation amblyopia subtypes, individual differences such as variation in the severity of the amblyogenic factor might be more important in determining pre-treatment vision than whether amblyopia was caused by refractive error, strabismus or both.

12.
Regen Biomater ; 11: rbae025, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38605853

RESUMEN

Wound repair is a complex physiological process that often leads to bacterial infections, which significantly threaten human health. Therefore, developing wound-healing materials that promote healing and prevent bacterial infections is crucial. In this study, the coordination interaction between sulfhydryl groups on dithiothreitol (DTT) and MoS2 nanosheets is investigated to synthesize a MoS2-DTT nanozyme with photothermal properties and an improved free-radical scavenging ability. Double-bond-modified hyaluronic acid is used as a monomer and is cross-linked with a PF127-DA agent. PHMoD is prepared in coordination with MoS2-DTT as the functional component. This hydrogel exhibits antioxidant and antibacterial properties, attributed to the catalytic activity of catalase-like enzymes and photothermal effects. Under the near-infrared (NIR), it exhibits potent antibacterial effects against gram-positive (Staphylococcus aureus) and gram-negative bacteria (Escherichia coli), achieving bactericidal rates of 99.76% and 99.42%, respectively. Furthermore, the hydrogel exhibits remarkable reactive oxygen species scavenging and antioxidant capabilities, effectively countering oxidative stress in L929 cells. Remarkably, in an animal model, wounds treated with the PHMoD(2.0) and NIR laser heal the fastest, sealing completely within 10 days. These results indicate the unique biocompatibility and bifunctionality of the PHMoD, which make it a promising material for wound-healing applications.

13.
Front Neurol ; 15: 1295788, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38645744

RESUMEN

Background: Docosahexaenoic acid (DHA) plays a crucial role in the growth and functional development of the infant brain. However, the impact of additional DHA supplementation on neurodevelopment in infants remains controversial in randomized controlled trials. In this systematic review and meta-analysis, we aimed to investigate the effects of prenatal and postnatal DHA supplementation on neurodevelopment. Methods: We systematically searched the MEDLINE, EMBASE, and Cochrane Library electronic databases using a predefined strategy until 8 February 2024. We extracted relevant study characteristics and outcomes related to the nervous system. Two independent reviewers critically evaluated the included studies to assess their validity and risk of bias. Results: A total of 21 studies met our inclusion criteria, one study was removed after quality assessment, and the meta-analysis included 9 randomized controlled trials. The meta-analysis results indicated that there was no statistically significant difference between the DHA supplementation group and the placebo group, as assessed by the Mental Development Index [MDI; mean difference (MD), 0.41; 95% confidence interval (CI), -0.91 to 1.73; p = 0.55]. However, the DHA group had a significantly higher Psychomotor Development Index (PDI) than the placebo group (MD, 1.47; 95% CI, 0.23 to 2.72; p = 0.02). Subgroup analyses based on populations showed that DHA supplementation was superior to placebo for infants in both MDI (language score conversion; MD, 2.05; 95% CI, -0.16 to 4.26; p = 0.07) and PDI (MD, 1.94; 95% CI, 0.23 to 3.65; p = 0.03). Other subgroup analyses indicated no statistical differences between the two groups. The remaining assessments that could not be summarized quantitatively underwent a narrative evaluation. Conclusion: Based on the BSID assessments, DHA supplementation in infants may have potential neurodevelopmental benefits. Because the meta-analysis included few high-quality articles and had some limitations, more relevant articles are needed to address the need for separate DHA supplementation in infants, pregnant women, and lactating mothers. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022348100, identifier: CRD42022348100.

14.
Photodermatol Photoimmunol Photomed ; 40(3): e12970, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38685665

RESUMEN

OBJECTIVE: Both piperine and a 308-nm excimer laser have significant curative effects on vitiligo. This study mainly explored the molecular mechanism of a 308-nm excimer combined with piperine in regulating melanocyte proliferation. METHODS: Epidermal melanocytes were cultured in piperine solution, and the cells were irradiated by an XTRAC excimer laser treatment system at 308-nm output monochromatic light. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were for detecting the expression levels of genes or proteins. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Transwell method was for assessing cell viability and migration capacity. The content of melanin was also detected. RESULTS: The combination of the 308-nm excimer laser and piperine enhanced the cell proliferation, migration, and melanin production of melanocytes and upregulated the level of miR-328, and restraint of miR-328 reversed the influence of the 308-nm excimer laser and piperine. Secreted frizzled-related protein 1 (SFRP1) is a direct target gene of miR-328, and miR-328 can inhibit the expression of SFRP1 and elevate the protein level of the Wnt/ß-catenin signaling pathway. CONCLUSION: The 308-nm excimer laser combined with piperine may be more efficient than piperine alone in the remedy of vitiligo, and the miR-328/SFRP1 and Wnt/ß-catenin pathways are participated in the proliferation, migration, and melanin synthesis of melanocytes.


Asunto(s)
Benzodioxoles , Movimiento Celular , Proliferación Celular , Melaninas , Piperidinas , Humanos , Alcaloides/farmacología , Benzodioxoles/farmacología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Melaninas/biosíntesis , Melanocitos/metabolismo , Melanocitos/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , MicroARNs/genética , MicroARNs/metabolismo , Piperidinas/farmacología , Alcamidas Poliinsaturadas/farmacología , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Rayos Láser , Vitíligo/tratamiento farmacológico , Vitíligo/terapia
15.
J Neurosci ; 44(11)2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38316563

RESUMEN

Cooling sensations arise inside the mouth during ingestive and homeostasis behaviors. Oral presence of cooling temperature engages the cold and menthol receptor TRPM8 (transient receptor potential melastatin 8) on trigeminal afferents. Yet, how TRPM8 influences brain and behavioral responses to oral temperature is undefined. Here we used in vivo neurophysiology to record action potentials stimulated by cooling and warming of oral tissues from trigeminal nucleus caudalis neurons in female and male wild-type and TRPM8 gene deficient mice. Using these lines, we also measured orobehavioral licking responses to cool and warm water in a novel, temperature-controlled fluid choice test. Capture of antidromic electrophysiological responses to thalamic stimulation identified that wild-type central trigeminal neurons showed diverse responses to oral cooling. Some neurons displayed relatively strong excitation to cold <10°C (COLD neurons) while others responded to only a segment of mild cool temperatures below 30°C (COOL neurons). Notably, TRPM8 deficient mice retained COLD-type but lacked COOL cells. This deficit impaired population responses to mild cooling temperatures below 30°C and allowed warmth-like (≥35°C) neural activity to pervade the normally innocuous cool temperature range, predicting TRPM8 deficient mice would show anomalously similar orobehavioral responses to warm and cool temperatures. Accordingly, TRPM8 deficient mice avoided both warm (35°C) and mild cool (≤30°C) water and sought colder temperatures in fluid licking tests, whereas control mice avoided warm but were indifferent to mild cool and colder water. Results imply TRPM8 input separates cool from warm temperature sensing and suggest other thermoreceptors also participate in oral cooling sensation.


Asunto(s)
Canales Catiónicos TRPM , Ratones , Masculino , Animales , Femenino , Canales Catiónicos TRPM/genética , Frío , Neuronas , Temperatura , Sensación Térmica/fisiología , Agua
16.
Front Neurol ; 15: 1343025, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38327621

RESUMEN

Background: Distal arthrogryposis type 5D (DA5D) represents a subtype of distal arthrogryposis (DA) characterized by congenital joint contractures in the distal extremities. DA5D is inherited in a rare autosomal recessive manner and is associated with the ECEL1 gene. In this report, we describe a case of an infant with bilateral knee contractures and ptosis, caused by a novel compound heterozygous mutation of ECEL1. Case presentation: We conducted DNA extraction, whole-exome sequencing analysis, and mutation analysis of ECEL1 to obtain genetic data on the patient. We subsequently analyzed the patient's clinical and genetic data. The proband was a 6 months-old male infant who presented with significant bilateral knee contracture disorders and bilateral ptosis. MRI demonstrated cartilage degradation in knee joint. Whole-exome sequencing of the patient's DNA revealed a compound heterozygous mutation of c.2152-15C>A and c.110_155del in ECEL1. Analysis with the MutationTaster application indicated that c.110_155del was pathogenic (probability = 1), causing frameshift mutations affecting 151 amino acids (p.F37Cfs*151). The truncated protein lost the substructure of a transmembranous site based on the predicted protein crystal structure AF-O95672-F1. The variant of c.2152-15C>A of ECEL1 was also predicted to be disease-causing (probability = 0.98) as it impaired the methylation of ECEL1 serving as an H3K27me3 modification site, which led to the dysfunction of the second topological domain. Therefore, we concluded that the compound heterozygous mutation caused the pathogenic phenotype of this proband. Conclusion: The present case highlights the usefulness of molecular genetic screening in diagnosing unexpected joint disorder. Identification of novel mutations in the ECEL1 gene broadens the mutation spectrum of this gene and adds to the genotype-phenotype map of DA5D. Furthermore, rapid whole-exome sequencing analysis enabled timely diagnosis of this rare disease, facilitating appropriate treatment and scheduled follow-up to improve clinical outcomes.

17.
Adv Sci (Weinh) ; 11(14): e2307920, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38308196

RESUMEN

Therapeutic cancer vaccines fail to produce satisfactory outcomes against solid tumors since vaccine-induced anti-tumor immunity is significantly hampered by immunosuppression. Generating an in situ cancer vaccine targeting immunological cold tumor microenvironment (TME) appears attractive. Here, a type of free-field based whole-body ultrasound (US)-driven nanovaccines are constructed, named G5-CHC-R, by conjugating the sonosensitizer, Chenghai chlorin (CHC) and the immunomodulator, resiquimod (R848) on top of a super small-sized dendrimeric nanoscaffold. Once entering tumors, R848 can be cleaved from a hypoxia-sensitive linker, thus modifying the TME via converting macrophage phenotypes. The animals bearing orthotopic pancreatic cancer with intestinal metastasis and breast cancer with lung metastasis are treated with G5-CHC-R under a free-field based whole-body US system. Benefit from the deep penetration capacity and highly spatiotemporal selectiveness, G5-CHC-R triggered by US represented a superior alternative for noninvasive irradiation of deep-seated tumors and magnification of local immune responses via driving mass release of tumor antigens and "cold-warm-hot" three-state transformation of TME. In addition to irradiating primary tumors, a robust adaptive anti-tumor immunity is potentiated, leading to successful induction of systemic tumor suppression. The sono-nanovaccines with good biocompatibility posed wide applicability to a broad spectrum of tumors, revealing immeasurable potential for translational research in oncology.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias , Animales , Nanovacunas , Ultrasonografía , Inmunidad Adaptativa , Adyuvantes Inmunológicos , Neoplasias/diagnóstico por imagen , Neoplasias/terapia
18.
Invest Ophthalmol Vis Sci ; 65(1): 3, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38165705

RESUMEN

Purpose: Intermittent exotropia (IXT) is the most common form of strabismus. Surgery can potentially improve binocular function in patients with IXT. We aimed to evaluate binocular function using a novel parameter-binocular summation ratio (BSR), measured using quantitative contrast sensitivity function (CSF) in patients with IXT before and after surgery. Methods: Prospective study of 63 patients with IXT and 41 healthy controls were consecutively enrolled and underwent quantitative CSF testing binocularly and monocularly. BSR was calculated by dividing the CSF of the binocular value by the better monocular value. Forty-eight patients with IXT underwent strabismus surgery. BSR, stereoacuity, fusion ability, and strabismus questionnaires were assessed pre-operatively and 2 months postoperatively. Results: Sixty-three patients with IXT (median age = 9 years) compared with 41 healthy controls showed a worse mean BSR based on all CSF metrics at baseline (the area under the log CSF [AULCSF], spatial frequency [SF] cutoff, and contrast sensitivity at 1.0-18.0 cpd SF). All 48 patients with IXT showed successful alignment after surgery, and there were significant improvements in BSR based on the AULCSF, SF cutoff, and contrast sensitivity at 6.0, 12.0, and 18.0 cpd SF, respectively. The distance stereoacuity and fusion ability also improved after surgery, and a better BSR was associated with better stereoacuity and fusion. For strabismus questionnaires, the psychosocial subscale scores improved postoperatively, whereas the functional subscale scores did not change. Conclusions: BSR based on quantitative CSF can characterize binocular function across a range of spatial frequencies and can be used as a supplemental measurement for monitoring binocularity in patients with IXT in clinical settings.


Asunto(s)
Exotropía , Estrabismo , Humanos , Niño , Exotropía/cirugía , Sensibilidad de Contraste , Visión Binocular , Estudios Prospectivos
19.
Transl Vis Sci Technol ; 13(1): 16, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38236190

RESUMEN

Purpose: Perceptual learning (PL) has shown promising performance in restoring visual function in adolescent amblyopes. We retrospectively compared the effect of a well-accepted PL paradigm on patients with anisometropic amblyopia with or without a patching therapy history (patching therapy [PT] group versus no patching therapy [NPT] group). Methods: Eighteen PT and 13 NPT patients with anisometropic amblyopia underwent monocular PL for 3 months. During training, patients practiced a Gabor detection task following the lateral masking paradigm by applying a temporal two-alternative forced choice procedure with the amblyopic eye. Monocular contrast sensitivity functions (CSF), visual acuity, interocular differences in visual function metrics, and stereoacuity were compared before and after training. Results: PL improved the visual acuity of the amblyopia eyes by 0.5 lines on average in the PT group and 1.5 lines in the NPT group. A significant reduction in the interocular difference in visual acuity was observed in the NPT group (P < 0.01) but not in the PT group (P = 0.05). Regarding CSF metrics, the area under the log CSF and cutoff in the amblyopic eyes of the NPT groups increased after training (P < 0.05). In addition, the interocular differences of the CSF metrics (P < 0.05) in the NPT group were significantly reduced. However, in the PT group, all the CSF metrics were unchanged after training. A total of 27 of 31 patients in both groups had no measurable stereopsis pretraining, and recovery after training was not significant. Conclusions: PL based on a lateral masking training paradigm improved visual function in anisometropic amblyopia. Patients without a patching history achieved greater benefits. Translational Relevance: PL based on a lateral masking training paradigm could be a new treatment for amblyopia.


Asunto(s)
Ambliopía , Adolescente , Humanos , Ambliopía/terapia , Estudios Retrospectivos , Ojo , Agudeza Visual
20.
Small Methods ; 8(3): e2301249, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38012517

RESUMEN

Proton exchange membrane fuel cells (PEMFCs) are gaining significant interest as an attractive substitute for traditional fuel cells, with higher energy density, lower environmental pollution, and better operation efficiency. However, the cathode reaction, i.e., the oxygen reduction reaction (ORR), is widely proved to be inefficient, and therefore an obstacle to the widespread development of PEMFCs. The requirement for affordable highly-efficient ORR catalysts is extremely urgent to be met, especially at fuel cell level. Unfortunately, most previous reports focus on the ORR performance at rotating disk electrodes (RDE) level instead of membrane electrode assembly (MEA) level, making it harder to evaluate ORR catalysts operating under real vehicle conditions. Obviously, it is extremely necessary to develop an in-depth understanding of the structure-activity relationship of highly-efficient ORR catalysts applied at MEA level. In this work, an overview of the latest advances in ORR catalysts is provided with an emphasis on their performance at MEA level, hoping to cover the novel and systemic insights for innovative and efficient ORR catalyst design and applications in PEMFCs.

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